Although advances in immunotherapy research have ushered in a new era of cancer treatment that tout the possibility of achieving curative outcomes in patients even with metastatic disease, strategies such as immune checkpoint blockade only demonstrate efficacious outcomes in select ‘immunogenic’ cancers. Immunogenicity in cancer is largely defined by antigenicity where higher mutational burden correlates with immune infiltration in the tumor, serving as a biomarker for response. For the vast majority of cancer, antigenicity falls short of the predictive margin, and these immunologically ‘cold’ tumors effectively circumvent immune surveillance mechanisms. Using colloidal nanoparticles as substrates, we create a multivalent bi-specific nanobioconjugate engager (mBiNE) that bridges the interaction between cancer cells and macrophages. Using simple conjugation chemistry, mBiNE exhibits a tumor receptor targeting antibody as well as an immune activating moiety- a method that is highly versatile and can be tailored to accustom unique cancer microenvironments. In this study we target mBiNE to human epidermal growth factor receptor 2 (HER2) on breast cancer cells, and simultaneously stimulate their phagocytic uptake with calreticulin (CRT) which interacts with lipoprotein receptor-related protein 1 (LRP1) on macrophages. We show that mBiNE directs recognition and clearance of cancer cells, and is capable of initiating adaptive immune responses that result in tumor clearance and durable anti-tumor immunity in syngeneic preclinical models.<br/>

Multivalent bi-specific nanobioconjugate engager for targeted cancer immunotherapy

256th National Meeting (2018)

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